**2.2 Regulation of vascular functions**

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

autonomic nerves and is considered a reversible disorder [10].

with CAN compared to those without CAN [14].

of many organs and cardiovascular autonomic dysfunction due to diabetic CAN is the most life-threatening condition [7]. Thus, CAN has been found associated with cardiac arrhythmias, silent myocardial infarction and sudden deaths in T2DM patients [8]. CAN progresses through a prolonged subclinical to clinical form [7, 9]. Clinical CAN or late stage CAN occurs due to both parasympathetic and sympathetic denervation of heart and it may be manifested by resting tachycardia, orthostatic hypotension, exercise intolerance and silent myocardial ischemia. But subclinical or early stage CAN is characterized by predominant damage to the vagus nerve innervating the heart with subsequent upper hand in sympathetic drive resulting in resting cardiac autonomic balance characterized by resting tachycardia [9]. However, sub-clinical CAN ensues largely from functional alteration of

Reduced HRV is the earliest sign of subclinical CAN [11]. HRV refers to a variation of RR intervals in time [12, 13]. HRV measured at rest is a marker of autonomic balance as well as cardiac sympathetic and parasympathetic tonic activity [13]. HRV is assessed through time domain, frequency domain and nonlinear metrics of electrocardiogram (ECG) recording [13]. HRV is reduced in type 2 diabetic patients

**2. Autonomic nervous system regulation of cardiovascular functions**

The main function of the heart is to pump blood into the closed circuit of circulation. The efficiency of this mechanical property of the heart depends on normal electrophysiology of the heart which per se depends on normal structural and functional integrity of sinus atrial node (SA node) and rest of the conducting system of the hear t. Autonomic nervous system plays crucial role in controlling both electrical and mechanical properties of the heart. However, the degree of influence of sympathetic and parasympathetic nerves on heart functions depends

Sympathetic nervous system via right and left cardiac nerves innervate atria and ventricles (including conducting system). Right cardiac nerve predominantly innervates SA node and it has more influence on heart rate (HR) and on the other hand left cardiac nerve predominantly controls myocardial contractility. Thus, the net effect of sympathetic stimulation is to increase HR, conduction velocity and strength of myocardial contractility. Parasympathetic nervous system through right and left vagus nerves innervate predominantly atrial muscle and very sparsely ventricular myocardium. Right vagus nerve primarily innervates the SA node and left vagus nerve innervates mainly atrio-ventricular node (AV node). Thus, the net effect of parasympathetic stimulation is to decrease HR and slightly decrease strength of heart contractility. Dynamic interaction occurs between sympathetic

on their abundance of innervation in different parts of the heart.

Autonomic nervous system (ANS), a portion of peripheral nervous system, has two subdivisions viz. sympathetic and parasympathetic nervous system. They are responsible for regulating the functions of almost organs of the body via visceral reflexes. Centrally, ANS activities or reflexes are integrated and controlled by hypothalamus, brain stem and spinal cord. Heart and blood vessels are innervated by sympathetic and parasympathetic nerve fibers. Thus, their functions are largely regulated by ANS apart from other regulating factors to adapt to different shortterm or long-term physiological/pathological changes of the internal environment

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of the body.

**2.1 Regulation of cardiac functions**

Arteries and veins are innervated only by sympathetic nerve fibers, whereas, capillaries do not have any autonomic nerve innervation. Thus, vasomotor tone of almost all blood vessels is mainly determined by sympathetic tone. Sympathetic stimulation causes vasoconstriction and vice versa. Parasympathetic nerve fibers do innervate some blood vessels of salivary glands, gastrointestinal glands and genital erectile tissues.
